Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway
Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway
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Acemannan 通过 AKT/mTOR 信号通路加速细胞增殖和皮肤伤口愈合
DOI：
10.1016/j.jdermsci.2015.03.016
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发表时间：
2015-08-01
影响因子：
4.6
通讯作者：
Xu, Xiang
中科院分区：
文献类型：
--
作者：
Xing, Wei;Guo, Wei;Xu, Xiang
背景：乙酰甘露聚糖是一种促进组织修复的生物活性多糖。目的：探讨乙酰甘露聚糖在皮肤创面愈合中的积极作用及其机制。方法：采用小鼠皮肤创伤模型和皮肤原代成纤维细胞模型，观察乙酰甘露聚糖对皮肤创面愈合的促进作用。观察乙酰甘露聚糖对成纤维细胞和小鼠成纤维细胞增殖核抗原Ki-67、细胞周期蛋白D1的表达及AKT/mTOR信号转导活性的影响。用雷帕霉素和AKT抑制剂研究AKT/mTOR信号通路在乙酰甘露聚糖促进皮肤创面愈合中的关键作用。结果：我们发现乙酰甘露聚糖显著促进皮肤创面闭合和细胞增殖。乙酰甘露聚糖可通过AKT/mTOR信号通路促进成纤维细胞周期蛋白D1的表达，从而增强真核细胞翻译起始因子4F(EIF4F)的活性，增加细胞周期蛋白D1的翻译。相反，mTOR抑制剂雷帕霉素或AKT抑制剂VIII阻断AKT/mTOR信号转导通路可阻断乙酰甘露聚糖诱导的细胞周期蛋白D1翻译和细胞增殖。体内研究证实，乙酰甘露聚糖激活AKT/mTOR在创面愈合中起关键作用，雷帕霉素可逆转这种作用。结论：乙酰甘露聚糖部分通过激活AKT/mTOR介导的蛋白质翻译机制促进皮肤创面愈合，有望成为皮肤创面治疗的新途径。(C)2015年由爱思唯尔爱尔兰有限公司代表日本皮肤病研究学会出版。
Background: Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear.Objective: The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism.Methods: Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing.Results: We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin.Conclusion: Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound. (C) 2015 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.